CN101863943B

CN101863943B - Crystallizing method of 5'-guanosine-monophosphate disodium salt

Info

Publication number: CN101863943B
Application number: CN201010210408.3A
Authority: CN
Inventors: 陈玉松; 陈玉平; 孙明贤; 李威
Original assignee: DALIAN ZHEN-AO BIO-ENGINEERING STOCK Co Ltd
Current assignee: DALIAN ZHEN-AO BIO-ENGINEERING STOCK Co Ltd
Priority date: 2010-06-28
Filing date: 2010-06-28
Publication date: 2014-03-12
Anticipated expiration: 2030-06-28
Also published as: CN101863943A

Abstract

The invention discloses a crystallizing method of a 5'-guanosine-monophosphate disodium salt, which has the advantages of simple operation as well as large crystalline particle, uniform particle, attractive fineness and high purity of products. The method comprises the following steps of: adding sodium hydroxide to a 5'-GMP aqueous solution of which the concentration is 5-40 percent; regulating the PH value of the solution to 7-11 and then adding absolute alcohol which has a PH value of 7-11 and is 0.5-3 times of the solution in volume and a catalyst; stirring at 15-80 DEG C to separate out 5'-GMP, 2Na; and centrifuging, washing and drying to obtain 5'-GMP, 2Na crystals, wherein the catalyst is a mixture of a 60-120 mesh siftage of 5'-guanosine-monophosphate disodium salt crystals and sodium carbonate, the mass ratio of the 60-120 mesh siftage of 5'-guanosine-monophosphate disodium salt crystals to the sodium carbonate is 1:2, and the addition quantity of the catalyst is 0.1-0.2 percent of the mass of the 5'-GMP.

Description

The crystallization method of 5'-GMP,2Na

Technical field:

The present invention relates to a kind of crystallization purifying method, especially a kind of simple to operate, product crystallization is large, the crystallization method of good fluidity, uniform particles, quality is attractive in appearance, purity is high 5'-GMP,2Na.

Background technology:

5 '-Nucleotide (CMP, AMP, UMP, GMP, IMP) be the product that RNA obtains through enzymic degradation, be widely used in just stipulating to add 5 '-Nucleotide in the international infant formula industry standards of field ，Ru such as medicine, chemical industry, food, healthcare products and agricultural, and the purity of 5 '-Nucleotide is an industrial difficult problem always.

At present, the method for purification of known 5'-GMP,2Na (5 '-GMP, 2Na) is conventional crystallization method, i.e. ethanol dissolved method.Be first with sodium hydroxide, to regulate 5 '-cyclic guanosine monophosphate solution of finite concentration, temperature, make it be alkalescence, and then add alcohol solvent to stir, make 5 '-GMP, 2Na separates out, and through centrifugal, washing and dry, obtains 5 '-GMP, 2Na crystal.Because alcohol solvent makes 5 '-GMP in solution, 2Na solubleness reduces, and causes 5 '-GMP, and the violent outburst of 2Na is separated out, and the product of separating out are white powder or the small-crystalline that viscosity is high, solid-liquid centrifugation difficulty.Products obtained therefrom exist particle inequality and water absorbability strong, the difficulty of sieving of easily uniting, the problem such as low and poor fluidity of purity.

Summary of the invention:

The present invention is the above-mentioned technical problem existing in order to solve prior art, provides a kind of simple to operate, and product crystallization is large, the crystallization method of good fluidity, uniform particles, quality is attractive in appearance, purity is high 5'-GMP,2Na.

Technical solution of the present invention is: a kind of crystallization method of 5'-GMP,2Na, it is characterized in that carrying out as follows: in the 5 '-GMP aqueous solution that is 5%～40% in concentration, add sodium hydroxide, adjusting solution pH value is 7～11, the dehydrated alcohol and the catalyzer that add 0.5～3 times of PH7～11 liquor capacity, be to stir under the condition of 15～80 ℃ in temperature again, makes 5 '-GMP, 2Na separates out, through centrifugal, washing and dry, obtain 5 '-GMP, 2Na crystal; Described catalyzer is the mixture of 5'-GMP,2Na crystal 60～120 order screen underflows and sodium carbonate, the mass ratio of 5'-GMP,2Na crystal 60～120 order screen underflows and sodium carbonate is 1: 2, and the addition of catalyzer is 1 of 5 '-GMP quality～2 ‰.

The present invention is in solution, to have added the catalyzer consisting of 5'-GMP,2Na crystal 60～120 order screen underflows and sodium carbonate with the maximum difference of prior art, improved ethanol to 5 '-GMP, the solubleness of 2Na, avoid 5 '-GMP, existing problem is separated out in the violent outburst of 2Na, gained 5 '-GMP, 2Na crystal is particulate state white macrocrystal, viscosity is low, solid-liquid separation is easy, product appearance is bright, uniform particles, good fluidity, be difficult for moisture absorption, can prevent the difficulty of sieving of uniting and existing because of moisture absorption, products obtained therefrom purity is high, through liquid chromatographic detection purity, be 98～102%, can be applicable to suitability for industrialized production

Embodiment:

Getting concentration is 5 '-guanosine monophosphate aqueous solution 1000L of 180g/L, with sodium hydroxide, is adjusted to PH7.5, then adds 2000L dehydrated alcohol and catalyzer, at 35 ℃, stirs, and makes 5 '-GMP, and 2Na separates out.Described catalyzer is the mixture of 5'-GMP,2Na crystal 60～120 order screen underflows and sodium carbonate, the mass ratio of 5'-GMP,2Na crystal 60～120 order screen underflows and sodium carbonate is 1: 2, and the addition of catalyzer is 1 of 5 '-GMP quality～2 ‰.Precipitate, after centrifugal solid-liquid separation, again with the white crystal of 85% washing with alcohol gained, dry, can obtain 5'-GMP sodium salt crystal 193.0kg.With liquid chromatograph, check that finished product purity is 99.4%, moisture 17%, last crystallization yield is 90%.

Detected result is as table 1:

Table 1

Test item	Standard	Embodiment of the present invention product
			Outward appearance	Should be white or off-white color crystallographic powder	White crystal
HPLC measures purity	97％～102％	99.4％
			Moisture (%)	15％～25％	17.0％
A250/260(PH7.0)	1.13～1.19	1.17
			A280/260(PH7.0)	0.64～0.68	0.66
PH	7.0～8.5	8.1
			Density (g/cm ³)	International standard is more than 0.45	0.65
Mobility (seeing explanation 1)	Be less than three beatings	Without patting
			Transmittance	More than 95%	97％
See through order number	60 order～120 orders	60～80 orders account for more than 95%

Illustrate 1: whether mobility needs to pat is judging criterion, be about to 5 '-GMP, 2Na fills the husky clock first half, then rely on gravity to make 5 '-GMP, 2Na flows vertically downward, in defluent process, need not pat husky clock is that mobility is best, and it is good patting (1-3 time) for few time, and repeatedly (more than 3 times) are that mobility is bad.

Claims

1. the crystallization method of a 5'-GMP,2Na, it is characterized in that carrying out as follows: in the 5 '-GMP aqueous solution that is 5%～40% in concentration, add sodium hydroxide, adjusting pH is 7～11, the dehydrated alcohol and the catalyzer that add 0.5～3 times of pH7～11 liquor capacity, be to stir under the condition of 15～80 ℃ in temperature again, makes 5 '-GMP, 2Na separates out, through centrifugal, washing and dry, obtain 5 '-GMP, 2Na crystal; Described catalyzer is the mixture of 5'-GMP,2Na crystal 60～120 order screen underflows and sodium carbonate, the mass ratio of 5'-GMP,2Na crystal 60～120 order screen underflows and sodium carbonate is 1: 2, and the addition of catalyzer is 1 of 5 '-GMP quality～2 ‰.